Absorption improvement of tranilast by forming highly soluble nano-size composite structures associated with α-glucosyl rutin via spray drying

Eur J Pharm Biopharm. 2015 May:92:49-55. doi: 10.1016/j.ejpb.2015.02.021. Epub 2015 Feb 26.

Abstract

Tranilast (TL) composite particles with α-glucosyl rutin (Rutin-G) were developed to improve the solubility and oral bioavailability of TL. Composite formulation of TL/Rutin-G was prepared using the spray-drying method, and their physicochemical properties were evaluated with respect to the morphology, particle size distribution, solubility and crystallinity. The nanostructure formation of Rutin-G was characterized by dynamic light scattering and transmission electron microscopy when Rutin-G or TL/Rutin-G spray-dried particles (SDPs) were introduced into water. A pharmacokinetic study was also performed to assess the improvement of oral absorption in rats. TL/Rutin-G SDPs were spherical particles with a diameter of 5.5μm. Even in the acidic condition, the remarkable improvement in solubility of TL was achieved, as evidenced by a 32.2-fold increase in solubility compared with untreated TL. The median size of Rutin-G nanostructures in water was 2nm. The formation of Rutin-G nanostructures and their drug inclusion properties may enhance the solubility and dissolution behavior of TL. A drastic increase was found in the exposure of TL in rats, with an increase in Cmax and AUC values of 114- and 36.4-fold, respectively, compared with those of untreated TL. These findings indicated that a TL formulation spray-dried with Rutin-G could enhance its solubility and absorption and thus its therapeutic properties.

Keywords: Composite; Nanostructure; Oral bioavailability; Spray-drying; Tranilast; α-Glucosyl rutin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Allergic Agents / administration & dosage*
  • Anti-Allergic Agents / chemistry
  • Anti-Allergic Agents / pharmacokinetics
  • Area Under Curve
  • Biological Availability
  • Chemistry, Pharmaceutical / methods
  • Crystallization
  • Dynamic Light Scattering
  • Male
  • Microscopy, Electron, Transmission
  • Nanocomposites
  • Nanoparticles*
  • Particle Size
  • Rats
  • Rats, Sprague-Dawley
  • Rutin / analogs & derivatives*
  • Rutin / chemistry
  • Solubility
  • Trisaccharides / chemistry*
  • Water / chemistry
  • ortho-Aminobenzoates / administration & dosage*
  • ortho-Aminobenzoates / chemistry
  • ortho-Aminobenzoates / pharmacokinetics

Substances

  • Anti-Allergic Agents
  • Trisaccharides
  • ortho-Aminobenzoates
  • Water
  • 4(G)-alpha-glucopyranosyl-rutin
  • Rutin
  • tranilast